EXCITABLE

TISSUES
-

Tissue, cell or membrane capable of undergoing

excitation (activation of atoms or molecules) in
response to an adequate stimulus.

2 Types:
1. Neuron or Nerve (anatomical unit)
-Cell Body, Dendrites, Axon



I.
Nervous System

2. Muscle Fiber (anatomical unit)

II.
Muscular System

a. Skeletal
b. Smooth
c. Cardiac

-Spinal Nerves: 31 pairs

*Cervical 8 pairs
*Thoracic 12 pairs Afferent
*Lumbar 5 pairs Efferent
*Sacral 5 pairs
*Coccyx 1 pair

General Functions of Nervous System:

a. Receives info from Sensory Organs
b. Processing and integration of info for an
appropriate response.
c. Control of Motor Functions of Body:
i.
Muscular Contraction
ii.
Rapid changes in Visceral events by
contraction of smooth muscles of
internal organs
iii.
Rates of secretion of some Endocrine
Glands

Subserved by the Physiologic Unit of the

Nervous System, The Reflex Arc and functions
like an electronic computer.

Basic Physiologic or Functional Unit of Nervous
System is the REFLEX ARC

2 Divisions:

A. Central Nervous System (CNS)
-Forebrain
-Midbrain
-Hindbrain
B. Peripheral Nervous System (PNS)

-Cranial Nerves: 12

Afferent
Efferent

What makes these tissues excitable?
MEMBRANE POTENTIAL

THE CELL MEMBRANE POTENTIAL
o

Existence of concentration gradients inside and

outside of cell membrane due to selective
permeability of cell membrane and factors that
influence diffusion.

When concentration gradients develop

electrical gradients also develop since most
elements in the body are ions. These electrical

potentials that develop will determine the cell

membrane potential.
o

Electrical potentials exist across cell membranes

of almost all cells but is most important in
excitable tissue (muscles and nerves) for the
purpose of impulse conduction. The difference
however is very fractional as not to disturb
nerve and muscle metabolism but enough to
cause excitation.

In other cells like glandular cells, macrophages

and ciliated cells, changes in membrane
potential play a role in controlling the cells
functions.

PROPERTIES OF THE CELL MEMBRANE

1. Na+ - K+ Leak Channels
100x more permeable to K+ giving a ratio of
K+ inside the cell membrane to outside of 35
to 1.

If one considers that cell membrane will
only allow K+ to diffuse because of the
concentration gradient, K+ will diffuse out
of the cell and leave behind an excess of (-)
ions.

**Although K+ leaks out of the cell, efflux is
limited because (+) Potential outside of the
cell membrane will repel further efflux of
K+.

DIFFUSION POTENTIAL

Potential gradients caused by ionic

concentration differences on either side of the
membrane.

Nernst Potential: diffusion potential across the
membrane that will oppose further diffusion of
a particular ion

-Microelectrode inserted into nerve fiber and recorded

membrane potential of approximately -90 mv at rest
(Resting Membrane Potential = normal membrane
potential of exciting tissues at rest)

Also according to the NERNST EQUATION,

when a concentration gradient coexists
with an electrical gradient, the electrical
potential that will stop the diffusion of an
ion across the cell membrane is called the
NERNST POTENTIAL and can be
determined by the NERNST EQUATION.

MEASURING THE CELL MEMBRANE POTENTIAL

**The NERNST POTENTIAL of K+ = -94 mv, so that at this
membrane potential, the efflux of K+ will stop.

Since leak channels also allow minute

diffusion of Na+ (Na+ will diffuse into the cell
membrane because of the concentration
gradient), the NERNST POTENTIAL that will
stop the influx of Na+ is calculated to be +61
mv.

 NERNST POTENTIAL, however, is only applicable if

the cell membrane is permeable to only 1 ion. In
reality, the cell membrane is permeable to many
ions. The electrical potential that will stop diffusion
of all ions involved will now be determined by the
GOLDMAN-HODGKIN-KATZ EQUATION which
states:

Importance of Pump

i.

Maintains Na+ and K+ concentration in the fluid

compartments

ii. Establishes (-) membrane potential

iii. Controls volume of cell

3. Selective Cell Membrane Permeability
-impermeable to organic intermediary products
of metabolism like SO4-, PO4- and CHONS

**Since Cl permeability does not change during
conduction of impulses, whereas permeability to Na+
and K+ changes, it will be Na+ and K+ that are going to be
primarily responsible for conduction so that Na+ and K+
gradients and permeability will be used in the equation.

Using the Goldman Equation, the electrical potential
of the cell membrane which will stop diffusion of Na+
& K+ is -86 mv which is closer to the Nernst Potential
of K+.

PRINCIPLE OF ELECTRICAL NEUTRALITY

-States that Everywhere, except adjacent to cell
membrane, the (+) and (-) charges are equal.
**For every (+) ion, there is a (-) ion nearby to
neutralize it, otherwise electrical potentials of
billions of volts would develop within fluids.

**This is expected because K+ is more

permeable across the cell membrane so that
diffusion of K+ will contribute more to the
membrane potential than the diffusion of Na+.
RMP however was recorded to be -90mv, what
factor now contributes to the -4 mv difference?
Consider the 2nd property of a cell membrane.

2. Na+ - K+ Electrogenic Pump

Pumps out 3Na+ and pumps in 2K+, leaving a net

deficit of (+) ions inside the cell membrane and
this contributes additional -4mv negativity to
the membrane potential of -86 mv giving now a
total of -90 mv as recorded.

-When (+) ions are pumped out or diffuse out of the

cell membrane, they line up along outside of the
membrane and the (-) ions left behind inside line up
along the inside of the membrane.
*Creates Dipole Layer out of (+) and (-) ions
outside and inside the cell membrane and thus
lipid-bilayer of the cell membrane functions as a
dieclectric capacitor and this is important in
impulse conduction because:
i. Only very small number of ions are needed to be
transferred through the cell membrane to establish
normal RMP of -90mv.

ii. Only very small numbers of (+) ions are needed to

diffuse into the cell membrane to reverse the
membrane potential to as much as +35 mv within
1/10,000 of a second.

IONIC BASIS OF ACTION POTENTIAL

**These changes are what happen during

impulse conduction or generation of the nerve
action potential.

Properties and Characteristics:

*Consider Voltage-Gated Na+ and K+ Channels

Voltage Gated Na+ Channels

1. Specific for Na+ Ions: 0.3 x 0.5 nm in diameter

2. Channels are negatively charged
3. Has 2 Voltage Gates:

a. Activation Gate:

- found outside of the cell membrane and
further gated by Ca++
- closed at RMP -90
-rapidly opens when the membrane
potential increases allowing influx of Na+
500-5,000 fold.
- Causes DEPOLARIZATION

*Blocked by toxin Tetrodotoxin (no impulse conduction
= paralysis)

NERVE ACTION POTENTIAL

b. Inactivation Gate:

-Means by which nerve signals are transmitted from

nerve to nerve (Synapse) or from nerve to muscle
(Neuromuscular Junction)

- found inside the cell membrane

- open at RMP -90 and closes slowly
10,0000th of a second after the increase in
membrane potential

*Rapid changes in membrane potential spread

rapidly along nerve fiber membrane.
*Changes in Resting Membrane Potential may be
caused by different types of stimuli: Thermal,
Electrical, Radiation, Pressure, Chemical etc.
Electrical Types:
I.

Cathodal : inject (-) ions to the surface of the

cell membrane

II. Anodal : inject (+) ions to the surface of the cell

membrane

*Disabled
by
pyrethrin
insecticides
(from
Chrysanthemums) so that inactivation gates remain
open.

VOLTAGE-GATED K+ CHANNEL:
Properties and Characteristics:
1. Specific for K+ ions; 0.3 x 0.3 nm diameter
2. Channel not charged
3. Has only 1 voltage gate:

- found inside of the cell membrane
- closed at RMP -90 and opens slowly when the
membrane potential increases efflux of K+.
-Causes REPOLARIZATION
-Remains open for duration of (+) membrane
potential and closes when membrane potential
is back to a very (-) value.

8. Resting Membrane State: return of normal Na+

and K+ distribution due to activation of
Electrogenic Na+-K+ Pump

*Blocked by Tetraethylammonium (K+ cannot leave the

cell; no conduction; no impulse = paralysis)

ROLE OF OTHER IONS

1. Impermeable Anions: responsible for the (-) charge
inside the cell membrane: PO4-, PO4-, CHONS and
other organic anions

***ACTION POTENTIAL graph Please refer
to Ganong for the series of events***

PHASES OF THE ACTION POTENTIAL:
1. Resting Membrane Potential (K+ inside, Na+
outside)

2. Stimulus Artifact; marks start of stimulus
applied to nerve

3. Latent Period: beginning depolarization until
Firing Level is reached

4. Firing Level: start of a Runway Potential or
Action Potential

5. Depolarization: Na+ influx thru Voltage gated
Na+ Activation Gates / slow closure of
inactivation Gates prevents further influx at
35mv

6. Repolarization: K+ efflux thru Voltage Gated K+
Channel when gate slowly opens during
depolarization

7. Hyperpolarization or Positive Under Potential
or Undershoot: due to continued leakage of K+
through the slow closing Voltage Gated K+
Channel and Na+-K+ Leak Channels until
Membrane Potential is down to -94mv (Nernst
Potential of K+)

2. CA++: presence of:

a. Ca++ Pump
- pumps Ca++ from the inside to the outside of
cell or into the Endoplasmic Reticulum.
- Causes Ca++ ion concentration gradient 10,000
fold: 10-7 molar inside and 10-3 molar outside

b. Voltage-Gated Ca++ Channels
- allows influx of of Ca++x and Na+ in smaller
amounts
- Slow channels, 10-20x longer for activation
gates
- Numerous in Cardia and Smooth Muscles

SOME PRINCIPLES:
*THRESHOLD STIMULUS: Minimum strength of stimulus
(voltage) needed to raise RMP of neuron to firing level,
usually by 15-30mv
*MAXIMAL STIMULUS: Minimum strength of stimulus
to fire all neurons in nerve trunk.
*ACCOMMODATION: Failure to fire a nerve despite of
raising strength of stimulus (voltage) due to:
a. Slow increase of internal voltage, over many
maximum stimuli instead of only a fraction of a second
b. Applying subthreshold stimulus, which gives the time
for slow inactivation gates of Na+ to close at same time
activating gates are opening.

**Also called Electrotonic Potential or
Generator Potential or Local Response or Acute
Subthreshold Potential
*NEERVE OR MUSCLE IMPULSE: transmission of the
depolarization process along a nerve or muscle fiber

*ALL OR NONE LAW: Depolarization travels over the

entire nerve so long as conditions are right OR none at
all if conditions are not right.

Proper conditions:
1. Threshold stimulus must be applied for proper
amount of time.
2. If subthreshold stimulus is applied, rate at which
voltage is increased must be rapid enough as not to
allow accommodation.

*DIRECTION OF PROPAGATION OF IMPULSE: Impulse
travels away from point of stimulus and over entire
nerve fiber and branches, in a UNIDIRECTIONAL
MANNER

UNIDIRECTIONAL FLOW OF IMPULSE DUE TO:
1. Local Circuit or Current Flow: Point of Na+
influx is called Current Sink and (+) charges are
carried 1-3 mm distance ahead causes
spontaneous opening of Na+ channels ahead. A
Positive Feedback leading to Vicious Cycle

2. Refractory Period of Cell Membrane: Period
when nerve membrane can not be depolarized.

CONDUCTION OF IMPULSES WHEN APPLIED ON THE

MIDDLE AXON:
*ORTHODROMIC CONDUCTION
-Direction of impulse goes toward telodendria where
neurotransmitter vesicles are stored. Impulse causes
release of neurotransmitter to propagate the impulse to
next neuron.
*ANTIDROMIC CONDUCTION
-Direction of impulse is toward dendritic end. Since
there are no stored neurotransmitters, impulse cannot
be propagated and dies out.

SALTATORY CONDUCTION
-Type of conduction in myelinated axons
-Since myelin is an effective insulator, current does not
flow thru it but instead travels from one node of
Ranvier to next.
-Current Sink at active Node of Ranvier electrotonically
depolarize the node ahead of the Action Potential.
-Depolarization jumps from one node to the next.
-Allows myelinated axons to conduct impulses 50x
faster than the fasted unmyelinated sheath.

2 Types:
1. Absolute Refractory Period (ARP)
-starts from FL to first 1/3 Repolarization Pd

Nerve absolutely cannot be fired
Mechanism: Inactivation of Voltage-Gated Na+
Channels or Ca++ Channels or both and no
amount of stimulus applied to these channels at
this period is able to open the gates.
In large myelinated nerves, lasts only , 500th of
a second.

2. Relative Refractory Period (RRP)

Occurs during last 2/3 of Repolarization period

During this period, nerve membrane can fire
but only if a Supra-threshold Stimulus is
applied.

**Wallerian Degeneration: Degeneration of nerve
distal to injury because of axoplasmic transport.

AXOPLASMIC TRANSPORT
-Transport of proteins and polypeptides from cell body
to the axonal ending thus maintaining functional and
anatomical integrity of axon.
-2 Types:
a. Orthograde Transport: from cell body toward axon
terminal and occur along microtubules that run along

length of axon with Dynein and Kinesin as Motor

Proteins
-Fast Transport: 400mm/day
-Slow Transport: 0.5-10mm/day

b. Retrogade Transport: from nerve ending to cell body
-Occurs along microtubules at about 200 mm/day
-Synaptic vesicles are recycled in terminal membrane
but some vesicles carried back to cell body and
deposited in lysosomes.
-Extracellular materials may be taken in by endocytosis:
ex. Nerve Growth Factor (NGF), viruses
-In some Dendrites, Mrna from cell body can be
transported in them and attach to specific ribosomes
where protein synthesis may take place.

SPEED OF CONDUCTION IS FASTER IF:
1. Diameter of nerve is bigger
2. Nerve is myelinated

*COMPOUND ACTION POTENTIAL
-Action potentials of all neurons in a nerve trunk